Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Drug Metabolism & Disposition
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Drug Metabolism & Disposition

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Visit dmd on Facebook
  • Follow dmd on Twitter
  • Follow ASPET on LinkedIn
Research ArticleArticle

Enantioselective Pharmacokinetics of Primaquine in Healthy Human Volunteers

Babu L. Tekwani, Bharathi Avula, Rajnish Sahu, Narayan D. Chaurasiya, Shabana I. Khan, Surendra Jain, Pius S. Fasinu, H.M.T. Bandara Herath, Donald Stanford, N.P. Dhammika Nanayakkara, James D. McChesney, Travis W. Yates, Mahmoud A. ElSohly, Ikhlas A. Khan and Larry A. Walker
Drug Metabolism and Disposition April 2015, 43 (4) 571-577; DOI: https://doi.org/10.1124/dmd.114.061127
Babu L. Tekwani
National Center for Natural Products Research (B.L.T., B.A., R.S., N.D.C., S.I.K., S.J., P.S.F., H.M.T.B.H., D.S., N.P.D.N., M.A.E., I.A.K., L.A.W.), Departments of BioMolecular Sciences (B.L.T., S.I.K., S.J., I.A.K., L.A.W.) and Pharmaceutics (M.A.E.), School of Pharmacy, and Department of Student Health Services (T.W.Y.), University of Mississippi, University; Ironstone Separations, Inc., Etta (J.D.M.); ElSohly Laboratories, Inc., Oxford (M.A.E.), Mississippi
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Bharathi Avula
National Center for Natural Products Research (B.L.T., B.A., R.S., N.D.C., S.I.K., S.J., P.S.F., H.M.T.B.H., D.S., N.P.D.N., M.A.E., I.A.K., L.A.W.), Departments of BioMolecular Sciences (B.L.T., S.I.K., S.J., I.A.K., L.A.W.) and Pharmaceutics (M.A.E.), School of Pharmacy, and Department of Student Health Services (T.W.Y.), University of Mississippi, University; Ironstone Separations, Inc., Etta (J.D.M.); ElSohly Laboratories, Inc., Oxford (M.A.E.), Mississippi
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rajnish Sahu
National Center for Natural Products Research (B.L.T., B.A., R.S., N.D.C., S.I.K., S.J., P.S.F., H.M.T.B.H., D.S., N.P.D.N., M.A.E., I.A.K., L.A.W.), Departments of BioMolecular Sciences (B.L.T., S.I.K., S.J., I.A.K., L.A.W.) and Pharmaceutics (M.A.E.), School of Pharmacy, and Department of Student Health Services (T.W.Y.), University of Mississippi, University; Ironstone Separations, Inc., Etta (J.D.M.); ElSohly Laboratories, Inc., Oxford (M.A.E.), Mississippi
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Narayan D. Chaurasiya
National Center for Natural Products Research (B.L.T., B.A., R.S., N.D.C., S.I.K., S.J., P.S.F., H.M.T.B.H., D.S., N.P.D.N., M.A.E., I.A.K., L.A.W.), Departments of BioMolecular Sciences (B.L.T., S.I.K., S.J., I.A.K., L.A.W.) and Pharmaceutics (M.A.E.), School of Pharmacy, and Department of Student Health Services (T.W.Y.), University of Mississippi, University; Ironstone Separations, Inc., Etta (J.D.M.); ElSohly Laboratories, Inc., Oxford (M.A.E.), Mississippi
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Shabana I. Khan
National Center for Natural Products Research (B.L.T., B.A., R.S., N.D.C., S.I.K., S.J., P.S.F., H.M.T.B.H., D.S., N.P.D.N., M.A.E., I.A.K., L.A.W.), Departments of BioMolecular Sciences (B.L.T., S.I.K., S.J., I.A.K., L.A.W.) and Pharmaceutics (M.A.E.), School of Pharmacy, and Department of Student Health Services (T.W.Y.), University of Mississippi, University; Ironstone Separations, Inc., Etta (J.D.M.); ElSohly Laboratories, Inc., Oxford (M.A.E.), Mississippi
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Surendra Jain
National Center for Natural Products Research (B.L.T., B.A., R.S., N.D.C., S.I.K., S.J., P.S.F., H.M.T.B.H., D.S., N.P.D.N., M.A.E., I.A.K., L.A.W.), Departments of BioMolecular Sciences (B.L.T., S.I.K., S.J., I.A.K., L.A.W.) and Pharmaceutics (M.A.E.), School of Pharmacy, and Department of Student Health Services (T.W.Y.), University of Mississippi, University; Ironstone Separations, Inc., Etta (J.D.M.); ElSohly Laboratories, Inc., Oxford (M.A.E.), Mississippi
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Pius S. Fasinu
National Center for Natural Products Research (B.L.T., B.A., R.S., N.D.C., S.I.K., S.J., P.S.F., H.M.T.B.H., D.S., N.P.D.N., M.A.E., I.A.K., L.A.W.), Departments of BioMolecular Sciences (B.L.T., S.I.K., S.J., I.A.K., L.A.W.) and Pharmaceutics (M.A.E.), School of Pharmacy, and Department of Student Health Services (T.W.Y.), University of Mississippi, University; Ironstone Separations, Inc., Etta (J.D.M.); ElSohly Laboratories, Inc., Oxford (M.A.E.), Mississippi
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
H.M.T. Bandara Herath
National Center for Natural Products Research (B.L.T., B.A., R.S., N.D.C., S.I.K., S.J., P.S.F., H.M.T.B.H., D.S., N.P.D.N., M.A.E., I.A.K., L.A.W.), Departments of BioMolecular Sciences (B.L.T., S.I.K., S.J., I.A.K., L.A.W.) and Pharmaceutics (M.A.E.), School of Pharmacy, and Department of Student Health Services (T.W.Y.), University of Mississippi, University; Ironstone Separations, Inc., Etta (J.D.M.); ElSohly Laboratories, Inc., Oxford (M.A.E.), Mississippi
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Donald Stanford
National Center for Natural Products Research (B.L.T., B.A., R.S., N.D.C., S.I.K., S.J., P.S.F., H.M.T.B.H., D.S., N.P.D.N., M.A.E., I.A.K., L.A.W.), Departments of BioMolecular Sciences (B.L.T., S.I.K., S.J., I.A.K., L.A.W.) and Pharmaceutics (M.A.E.), School of Pharmacy, and Department of Student Health Services (T.W.Y.), University of Mississippi, University; Ironstone Separations, Inc., Etta (J.D.M.); ElSohly Laboratories, Inc., Oxford (M.A.E.), Mississippi
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
N.P. Dhammika Nanayakkara
National Center for Natural Products Research (B.L.T., B.A., R.S., N.D.C., S.I.K., S.J., P.S.F., H.M.T.B.H., D.S., N.P.D.N., M.A.E., I.A.K., L.A.W.), Departments of BioMolecular Sciences (B.L.T., S.I.K., S.J., I.A.K., L.A.W.) and Pharmaceutics (M.A.E.), School of Pharmacy, and Department of Student Health Services (T.W.Y.), University of Mississippi, University; Ironstone Separations, Inc., Etta (J.D.M.); ElSohly Laboratories, Inc., Oxford (M.A.E.), Mississippi
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
James D. McChesney
National Center for Natural Products Research (B.L.T., B.A., R.S., N.D.C., S.I.K., S.J., P.S.F., H.M.T.B.H., D.S., N.P.D.N., M.A.E., I.A.K., L.A.W.), Departments of BioMolecular Sciences (B.L.T., S.I.K., S.J., I.A.K., L.A.W.) and Pharmaceutics (M.A.E.), School of Pharmacy, and Department of Student Health Services (T.W.Y.), University of Mississippi, University; Ironstone Separations, Inc., Etta (J.D.M.); ElSohly Laboratories, Inc., Oxford (M.A.E.), Mississippi
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Travis W. Yates
National Center for Natural Products Research (B.L.T., B.A., R.S., N.D.C., S.I.K., S.J., P.S.F., H.M.T.B.H., D.S., N.P.D.N., M.A.E., I.A.K., L.A.W.), Departments of BioMolecular Sciences (B.L.T., S.I.K., S.J., I.A.K., L.A.W.) and Pharmaceutics (M.A.E.), School of Pharmacy, and Department of Student Health Services (T.W.Y.), University of Mississippi, University; Ironstone Separations, Inc., Etta (J.D.M.); ElSohly Laboratories, Inc., Oxford (M.A.E.), Mississippi
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mahmoud A. ElSohly
National Center for Natural Products Research (B.L.T., B.A., R.S., N.D.C., S.I.K., S.J., P.S.F., H.M.T.B.H., D.S., N.P.D.N., M.A.E., I.A.K., L.A.W.), Departments of BioMolecular Sciences (B.L.T., S.I.K., S.J., I.A.K., L.A.W.) and Pharmaceutics (M.A.E.), School of Pharmacy, and Department of Student Health Services (T.W.Y.), University of Mississippi, University; Ironstone Separations, Inc., Etta (J.D.M.); ElSohly Laboratories, Inc., Oxford (M.A.E.), Mississippi
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ikhlas A. Khan
National Center for Natural Products Research (B.L.T., B.A., R.S., N.D.C., S.I.K., S.J., P.S.F., H.M.T.B.H., D.S., N.P.D.N., M.A.E., I.A.K., L.A.W.), Departments of BioMolecular Sciences (B.L.T., S.I.K., S.J., I.A.K., L.A.W.) and Pharmaceutics (M.A.E.), School of Pharmacy, and Department of Student Health Services (T.W.Y.), University of Mississippi, University; Ironstone Separations, Inc., Etta (J.D.M.); ElSohly Laboratories, Inc., Oxford (M.A.E.), Mississippi
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Larry A. Walker
National Center for Natural Products Research (B.L.T., B.A., R.S., N.D.C., S.I.K., S.J., P.S.F., H.M.T.B.H., D.S., N.P.D.N., M.A.E., I.A.K., L.A.W.), Departments of BioMolecular Sciences (B.L.T., S.I.K., S.J., I.A.K., L.A.W.) and Pharmaceutics (M.A.E.), School of Pharmacy, and Department of Student Health Services (T.W.Y.), University of Mississippi, University; Ironstone Separations, Inc., Etta (J.D.M.); ElSohly Laboratories, Inc., Oxford (M.A.E.), Mississippi
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF + SI
  • PDF
Loading

Abstract

Primaquine (PQ), a racemic drug, is the only treatment available for radical cure of relapsing Plasmodium vivax malaria and blocking transmission of P. falciparum malaria. Recent studies have shown differential pharmacologic and toxicologic profiles of individual PQ enantiomers in rodent, dog, and primate animal models. This study was conducted in six healthy adult human volunteers to determine the plasma pharmacokinetic profile of enantiomers of PQ and carboxyprimaquine (cPQ), the major plasma metabolite. The individuals were orally administered PQ diphosphate, equivalent to 45-mg base, 30 minutes after a normal breakfast. Blood samples were collected at different time intervals, and plasma samples were analyzed for enantiomers of PQ and cPQ. Plasma PQ concentrations were low and variable for both parent enantiomers and peaked around 2-4 hours. Peak (−)-(R)-PQ concentrations ranged from 121 ng/ml to 221 ng/ml, and peak (+)-(S)-PQ concentrations ranged from 168 ng/ml to 299 ng/ml. The cPQ concentrations were much higher and were surprisingly consistent from subject to subject. Essentially all the cPQ detected in plasma was (−)-cPQ. The peak concentrations of (−)-cPQ were observed at 8 hours (range: 1104-1756 ng/ml); however, very high concentrations were sustained through 24 hours. (+)-cPQ was two orders of magnitude lower than (−)-cPQ, and in a few subjects it was detected but only under the limit of quantification. In vitro studies with primary human hepatocytes also suggested more rapid metabolism of (−)-PQ compared with (+)-PQ. The results suggest more rapid metabolism of (−)-PQ to (−) cPQ compared with (+)-PQ. Alternatively, (+)-PQ or (+)-cPQ could be rapidly converted to another metabolite(s) or distributed to tissues. This is the first clinical report on enantioselective pharmacokinetic profiles of PQ and cPQ and supports further clinical evaluation of individual PQ enantiomers.

Footnotes

    • Received September 10, 2014.
    • Accepted January 30, 2015.
  • This study was supported in part by the Bill & Melinda Gates Foundation through a Grand Challenge Award [OPP53288]. The National Center for Natural Products Research is supported by the U.S. Department of Agriculture Agricultural Research Service scientific cooperative agreement [58-6408-2-0009].

  • dx.doi.org/10.1124/dmd.114.061127.

  • ↵Embedded ImageThis article has supplemental material available at dmd.aspetjournals.org.

  • Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics
View Full Text

 

DMD articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Drug Metabolism and Disposition: 43 (4)
Drug Metabolism and Disposition
Vol. 43, Issue 4
1 Apr 2015
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Editorial Board (PDF)
  • Front Matter (PDF)
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Drug Metabolism & Disposition article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Enantioselective Pharmacokinetics of Primaquine in Healthy Human Volunteers
(Your Name) has forwarded a page to you from Drug Metabolism & Disposition
(Your Name) thought you would be interested in this article in Drug Metabolism & Disposition.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleArticle

Primaquine Enantiomers Pharmacokinetics in Humans

Babu L. Tekwani, Bharathi Avula, Rajnish Sahu, Narayan D. Chaurasiya, Shabana I. Khan, Surendra Jain, Pius S. Fasinu, H.M.T. Bandara Herath, Donald Stanford, N.P. Dhammika Nanayakkara, James D. McChesney, Travis W. Yates, Mahmoud A. ElSohly, Ikhlas A. Khan and Larry A. Walker
Drug Metabolism and Disposition April 1, 2015, 43 (4) 571-577; DOI: https://doi.org/10.1124/dmd.114.061127

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Research ArticleArticle

Primaquine Enantiomers Pharmacokinetics in Humans

Babu L. Tekwani, Bharathi Avula, Rajnish Sahu, Narayan D. Chaurasiya, Shabana I. Khan, Surendra Jain, Pius S. Fasinu, H.M.T. Bandara Herath, Donald Stanford, N.P. Dhammika Nanayakkara, James D. McChesney, Travis W. Yates, Mahmoud A. ElSohly, Ikhlas A. Khan and Larry A. Walker
Drug Metabolism and Disposition April 1, 2015, 43 (4) 571-577; DOI: https://doi.org/10.1124/dmd.114.061127
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Introduction
    • Material and Methods
    • Results
    • Discussion
    • Acknowledgments
    • Authorship Contributions
    • Footnotes
    • Abbreviations
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF + SI
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • In Vivo Functional Effects of CYP2C9 M1L
  • Clearance pathways: fevipiprant with probenecid perpetrator
  • Predicting Volume of Distribution from In Vitro Parameters
Show more Articles

Similar Articles

  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About DMD
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Journal of Pharmacology and Experimental Therapeutics
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-009X (Online)

Copyright © 2021 by the American Society for Pharmacology and Experimental Therapeutics